The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

ASCO 2016 - Other therapies after failing Pembro...and...trial with OX40 - alone and with Pembro...still enrolling....

Background: Blockade of programmed death
(PD-1) receptor has shown unprecedented rates of durable clinical responses in
patients with metastatic melanoma. However, the majority of patients eventually
progress on anti-PD-1 therapy. Currently, there is no standard strategy guiding
the treatment in this setting, partly due to the lack of knowledge of the clinical
course after PD-1 blockade failure. Methods: We retrospectively reviewed
140 patients with metastatic melanoma treated with pembrolizumab at Mayo
Clinic, Rochester, between January 1, 2012 and November 1, 2015, identifying 70
patients who failed pembrolizumab treatment (due to disease progression or
toxicity). The clinical outcomes and RECIST objective response rates (ORR) to
treatments received after pembrolizumab were assessed. Results: Of the
70 patients who failed pembrolizumab therapy, 48 received further systemic
therapies. Of these, 43 had complete follow-up data and were included in our
analysis. Thirty patients received 1 line of subsequent therapy; while 13
patients received multiple subsequent treatments (average 2.5). Eighteen
patients with a BRAF mutation received targeted therapy, 9 of whom received
targeted therapy alone, with an ORR of 55.6% and 0% stable disease (SD). Nine
of these 18 BRAF mutant patients received targeted therapy combined with
chemotherapy and/or immunotherapy, with an ORR of 22.2% and 33.3% SD. Twenty
two of the 43 patients received immunotherapy (nivolumab and/or ipilimumab or
pembrolizumab)-based treatment (alone or in combination with chemotherapy),
with an ORR of 31.8%, and 13.6% SD. Nineteen of the 43 patients received
chemotherapy alone with an ORR of 26.3% and 0% SD. Conclusions:Patients
with metastatic melanoma who failed previous pembrolizumab therapy appear to
benefit from further systemic treatments, including additional immunotherapy.
Combination therapies show favorable clinical outcomes. The biological
mechanism of combining PD-1 blockade with other therapy modalities is currently
being studied and will further improve patient outcomes.

As was mentioned in the last link....here is a report on OX40 alone and with pembro....still enrolling...

ENGAGE-1:
A first in human study of the OX40 agonist GSK3174998 alone and in combination
with pembrolizumab in patients with advanced solid tumors.ASCO 2016.# TPS3107.J Clin Oncol 34, 2016.Infante, Ahlers, Hodi, et al.

Background:
OX40 (CD134) is a potent costimulatory tumor necrosis factor receptor expressed
on activated CD4+ and CD8+ T cells. OX40 agonism promotes T-cell division and
survival, resulting in stimulation of both immune effector and memory
functions, while also blocking the suppressive function of regulatory T cells.
This holds potential to overcome immune resistance and enhance immune mediated
anti-tumor activity with OX40 agonism, particularly in combination with
checkpoint inhibition. GSK3174998 is a humanized IgG1 anti-OX40 agonistic
monoclonal antibody identified through collaboration with MD Anderson Cancer
Center and is currently in phase I development. Methods: This is an
open-label, non-randomized, multicenter study of GSK3174998 administered alone
and in combination with pembrolizumab in patients (pts) with selected advanced
or recurrent solid tumors: non-small cell lung cancer, squamous cell carcinoma
of the head and neck, renal cell carcinoma, melanoma, bladder, soft tissue
sarcoma, triple-negative breast cancer, and colorectal carcinoma displaying
microsatellite instability. The study will be conducted in 2 parts in
approximately 180 pts. Primary objectives are to determine safety,
tolerability, and maximum tolerated or administered dose of GSK3174998 as a
single agent (Part 1) and when administered in combination with 200 mg
pembrolizumab (Part 2). Secondary objectives include evaluation of antitumor
activity, response rate and duration, progression-free survival, and overall
survival, pharmacokinetics, pharmacodynamic activity in the blood and tumor
microenvironment, and immunogenicity. Adverse events will be monitored using
NCI CTCAE v. 4.0. Radiographic imaging will be obtained every 12 weeks to
assess clinical response defined by immune-related RECIST. Tumor biopsies and
blood samples will be collected before and during treatment to allow
investigation of candidate biomarkers which may predict clinical response. As
of Feb 1, 2016, Cohorts 1 and 2 have completed without DLT and enrollment to
Cohort 3 is ongoing. Clinical trial information: NCT02528357